Nilotinib 300 mg BID in Newly Diagnosed CP-CML Patients to Verify Disappearance of CD34+/Lin-Ph+ Cells

NCT01856283 | Completed Phase 2

• 1 other identifier: PhilosoPhy34 CAMN107EIT11T
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 17

Brief Summary

This is a multicentre, single-arm study of nilotinib 300 mg BID in newly diagnosed patients with CP-CML. This study is designed to establish the disappearance of Ph+ stem cells (CD34+/lin-) in BM during nilotinib treatment. In addition, in this study the investigators aim to perform Gene Expression Profiling (GEP) of CML enrolled patients using Affymetrix GeneChip Instruments and Software Systems, and Affymetrix GeneChip Human Genome U133 Plus 2.0 (whole human transcriptome analysis) at diagnosis and at 3 different time points during treatment with Nilotinib (after 3, 6, 12 months).

Conditions

Leukemia, Myeloid, Chronic-Phase

Outcome Measures

Primary Outcomes (1)

• CD34+/lin-Ph+ cells

  To measure the rate of CD34+/lin-Ph+ cells in the BM after 6 months of treatment. In order to obtain this result, BM blood of all enrolled patients (see Appendix 1\) will be stored after 6 months of treatment with nilotinib. The isolated CD34+/lin- cells will be employed for standard FISH analysis.

  6 month

Secondary Outcomes (1)

• CD34+/lin- cells (composite measure)

  12 month

Study Arms (1)

Nilotinib

EXPERIMENTAL

study of nilotinib 300 mg BID

Drug: Nilotinib 300mg BID

Interventions

Nilotinib 300mg BID DRUG

Nilotinib

Also known as: Nilotinib

Nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of Ph chromosome (9;22) translocation within 3 months of diagnosis
• Patients Ph negative or with variant translocations by standard cytogenetic analysis but Ph positive by FISH, are eligible as well
• Age ≥ 18 years old (no upper age limit given)
• WHO performance status ≤2
• Normal serum levels ≥ LLN (lower limit of normal) of potassium, magnesium, total calcium corrected for serum albumin or phosphorus, or correctable to within normal limits with supplements, prior to the first dose of study medication
• AST and ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if considered due to leukaemia
• Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukaemia
• Total bilirubin ≤ 1.5 x ULN, except know Mb Gilbert
• Serum lipase and amylase ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN
• Written informed consent signed prior to any study procedures being performed

You may not qualify if:

• Pre-treatment with HU for \> 3 months and with imatinib is not permitted
• Prior accelerated phase including clonal evolution or blast crisis
• Contraindication to excipients in study medication
• impaired cardiac function including any of the following:
• LVEF \<45%
• Complete left bundle branch block
• Right bundle branch block plus left anterior hemiblock,bifascicular block
• Use of a ventricular-paced pacemaker
• Congenital long QT syndrome
• Clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (\<50 beats per minute)
• QTcF \>450 msec on screening ECG.If QTcF \>450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion
• Myocardial infarction within 12 months prior to starting nilotinib
• Other clinical significant heart disease (e.g. unstable angina,congestive heart failure,uncontrolled hypertension)
• Acute (i.e. within 1 year of starting study medication) or chronic pancreatitis

Sponsors & Collaborators

• Niguarda Hospital: lead

Study Sites (17)

A.O. Ospedale S. Antonio

Gallarate, Milano, Italy

Location

Ospedale Desio- "Ospedale Civile" di Vimercate, Desio, Carate Brianza, Giussano, Seregno.

Vimercate, Milano, Italy

Location

A.O di Circolo di Busto Arsizio

Busto Arsizio, Varese, Italy

Location

Ospedali Riuniti Bergamo

Bergamo, Italy

Location

Spedali Civili Brescia

Brescia, Italy

Location

Ospedale Valduce

Como, Italy

Location

Istituti Ospitalieri di Cremona

Cremona, Italy

Location

A.O Ospedale Lecco

Lecco, Italy

Location

Ospedale San Raffaele

Milan, Italy, Italy

Location

A.O Sacco

Milan, Italy

Location

Istituto dei Tumori

Milan, Italy

Location

Istituto Europeo Oncologia

Milan, Italy

Location

Ospedale Maggiore Policlinico

Milan, Italy

Location

Ospedale S. Paolo

Milan, Italy

Location

S. Gerardo di Monza

Monza, Italy

Location

Policlinico S.Matteo Pavia

Pavia, Italy

Location

A.O. Universitaria Fondazione Macchi

Varese, Italy

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase

Interventions

nilotinib; BID protein, human

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ester Pungolino, MD

  Niguarda Ca' Granda Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: May 17, 2013
• Study Start: March 1, 2013
• Primary Completion: July 1, 2020
• Study Completion: January 1, 2021
• Last Updated: January 13, 2021

Record last verified: 2021-01

Locations

IT (17)